Chronic kidney disease (CKD) and its metabolic derangements substantially affect the well-being of children. In order to define the nature, magnitude, and temporal evolution of the adverse effects of progressive CKD, we propose to extend the follow-up of the Prospective Study of the Chronic Kidney Disease in Children (CKiD) to determine (1) risk factors for accelerated decline;(2) factors contributing to abnormalities of growth and associated morbidity;(3) prevalence of risk factors for cardiovascular disease;and (4) impact on neurocognitive abilities, social-behavioral functioning and quality of life. The CKiD is a cooperative effort of a Data Coordinating Center, a Central Biochemistry Lab and two Clinical Coordinating Centers (CCC's) that oversee subject recruitment and retention at 44 participating clinical sites in the US and Canada. Since study initiation in Oct 2003, we finalized and implemented a common protocol at 44 sites, met our recruitment goal of 540 children, aged 1 to <= 16 yrs with estimated glomerular filtration rate (GFR) 30-90 ml/min/1.73m2 formula and have successfully retained the cohort to date. At enrollment, 6 month and annual visits thereafter, selected exposures are obtained on participants, including sociodemographic characteristics, family history, healthcare utilization, environmental exposures and medication use using standardized questionnaires. Standardized blood pressure, growth and nutritional assessments, metabolic status, measures of anemia, dyslipidemia, microinflammation, and proteinuria are also measured. Level of kidney function (GFR) is measured annually for 2 years then every other year by plasma disappearance of iohexol. The primary outcomes of interest is the temporal evolution of subclinical measures and clinical events associated with CKD progression as measured by decline in GFR, growth failure and its treatment, neurocognitive and behavioral deficits and cardiovascular disease, specified in our aims. Potential analyses that will be conducted using the CKiD infrastructure to explore risk-factor disease relationships include traditional prospective cohort analyses where putative risk factors are measured in participants at baseline; nested case-control studies in which laboratory studies are performed on stored baseline specimens in cases (e.g.rapid progressors) and appropriately matched controls (e.g.non-progressors);and cross-cohort analyses utilizing parallel cohorts.